Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
June-2017 Volume 50 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 50 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4

  • Authors:
    • Yunzhi Pan
    • Xiong Shu
    • Lichao Sun
    • Long Yu
    • Lixin Sun
    • Zhihua Yang
    • Yuliang Ran
  • View Affiliations / Copyright

    Affiliations: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang, Beijing 100021, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1965-1976
    |
    Published online on: April 19, 2017
       https://doi.org/10.3892/ijo.2017.3965
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multilineage differentiation potential. Clinical evidence suggests that CSCs in a tumor mass are the cellular determinants to promote cancer invasion and metastasis. MicroRNAs (miRNAs) have emerged as important modulators of cancer stem cell characteristics. Unveiling the candidate miRNAs that regulate CSCs may provide novel therapeutic targets against cancer. We analyzed the miRNA expression profiles regulating the cancer stem-like cell characteristics in gastric cancer. Gastric cancer stem cells (GCSCs) were sorted using the stem cell marker CD44 by fluorescence-activated cell sorting. Functional studies revealed that CD44(+) cells formed more sphere colonies and showed higher invasiveness than CD44(-) cells. miRNA microarray analysis revealed that miR‑196a‑5p was significantly upregulated in CD44(+) cells than CD44(-) cells. Suppression of miR‑196a‑5p led to decreased colony formation and invasion of GCSCs. miR‑196a‑5p decreased the expression of Smad4 by targeting 3'-UTR of the mRNA. The expression of Smad4 in gastric cancer tissues was correlated with differentiation state of tumors, TNM stage and depth of invasion. The stimulation of epithelial-mesenchymal transition (EMT) by miR‑196a‑5p in cancer stem-like cells was abolished by overexpression of Smad4. Collectively, these data demonstrate that miR‑196a‑5p has a key role in EMT and invasion by targeting Smad4 in GCSCs. miR‑196a‑5p may serve as a potential target for gastric cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Chen W, Zheng R, Zhang S, Zhang S, Zhao P, Li G, Wu L and He J: Report of incidence and mortality in China cancer registries, 2009. Chin J Cancer Res. 25:10–21. 2013.PubMed/NCBI

3 

Kim TH and Shivdasani RA: Stomach development, stem cells and disease. Development. 143:554–565. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Jordan CT, Guzman ML and Noble M: Cancer stem cells. N Engl J Med. 355:1253–1261. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Zhang X, Hua R, Wang X, Huang M, Gan L, Wu Z, Zhang J, Wang H, Cheng Y and Li J: Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer. Oncotarget. 7:9815–9831. 2016.PubMed/NCBI

6 

Alison MR, Lin WR, Lim SM and Nicholson LJ: Cancer stem cells: In the line of fire. Cancer Treat Rev. 38:589–598. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Liu TJ, Sun BC, Zhao XL, Zhao XM, Sun T, Gu Q, Yao Z, Dong XY, Zhao N and Liu N: CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene. 32:544–553. 2013. View Article : Google Scholar

8 

Sakakini N, Turchi L, Bergon A, Holota H, Rekima S, Lopez F, Paquis P, Almairac F, Fontaine D, Baeza-Kallee N, et al: A positive feed-forward loop associating EGR1 and PDGFA promotes proliferation and self-renewal in glioblastoma stem cells. J Biol Chem. 291:10684–10699. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Nataraj SM, Prema CL, Vimalambike MG, Shivalingaiah SC, Sundaram S, Kumar AP, Math AK and Prashant A: Major protein of carcinoembryonic antigen gene family - CD66c, a novel marker in colon carcinoma. J Clin Diagn Res. 10:XC01–XC04. 2016.PubMed/NCBI

10 

Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J, Chen R and Zhou Y: Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties. Int J Oncol. 42:453–459. 2013.

11 

Takebe N, Harris PJ, Warren RQ and Ivy SP: Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 8:97–106. 2011. View Article : Google Scholar

12 

Sounni NE and Noel A: Targeting the tumor microenvironment for cancer therapy. Clin Chem. 59:85–93. 2013. View Article : Google Scholar

13 

Lim YC, Kang HJ, Kim YS and Choi EC: All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by suppression of Wnt/β-catenin pathway. Eur J Cancer. 48:3310–3318. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS and Sun D: Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 16:2580–2590. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Yang T and Rycaj K: Targeted therapy against cancer stem cells. Oncol Lett. 10:27–33. 2015.PubMed/NCBI

16 

Leon G, MacDonagh L, Finn SP, Cuffe S and Barr MP: Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways. Pharmacol Ther. 158:71–90. 2016. View Article : Google Scholar

17 

Lau WM, Teng E, Chong HS, Lopez KA, Tay AY, Salto-Tellez M, Shabbir A, So JB and Chan SL: CD44v8-10 is a cancer-specific marker for gastric cancer stem cells. Cancer Res. 74:2630–2641. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Mansour SF and Atwa MM: Clinicopathological significance of CD133 and ALDH1 cancer stem cell marker expression in invasive ductal breast carcinoma. Asian Pac J Cancer Prev. 16:7491–7496. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Nishikawa S, Konno M, Hamabe A, Hasegawa S, Kano Y, Fukusumi T, Satoh T, Takiguchi S, Mori M, Doki Y, et al: Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26. Oncol Lett. 9:2361–2367. 2015.PubMed/NCBI

20 

Tseng JY, Yang CY, Yang SH, Lin JK, Lin CH and Jiang JK: Circulating CD133(+)/ESA(+) cells in colorectal cancer patients. J Surg Res. 199:362–370. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Shitara K, Doi T, Nagano O, Imamura CK, Ozeki T, Ishii Y, Tsuchihashi K, Takahashi S, Nakajima TE, Hironaka S, et al: Dose-escalation study for the targeting of CD44v cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer. 20:341–349. 2017. View Article : Google Scholar

22 

Wang W, Dong LP, Zhang N and Zhao CH: Role of cancer stem cell marker CD44 in gastric cancer: A meta-analysis. Int J Clin Exp Med. 7:5059–5066. 2014.

23 

Takahashi RU, Miyazaki H and Ochiya T: The role of microRNAs in the regulation of cancer stem cells. Front Genet. 4:2952014. View Article : Google Scholar : PubMed/NCBI

24 

Liu C and Tang DG: MicroRNA regulation of cancer stem cells. Cancer Res. 71:5950–5954. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Ma C, Huang T, Ding YC, Yu W, Wang Q, Meng B and Luo SX: MicroRNA-200c overexpression inhibits chemoresistance, invasion and colony formation of human pancreatic cancer stem cells. Int J Clin Exp Pathol. 8:6533–6539. 2015.PubMed/NCBI

26 

Yu D, Shin HS, Lee YS and Lee YC: miR-106b modulates cancer stem cell characteristics through TGF-β/Smad signaling in CD44-positive gastric cancer cells. Lab Invest. 94:1370–1381. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Wu Q, Yang Z, Wang F, Hu S, Yang L, Shi Y and Fan D: MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells. J Cell Sci. 126:4220–4229. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y and Wang TC: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27:1006–1020. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Xu H, Tian Y, Yuan X, Wu H, Liu Q, Pestell RG and Wu K: The role of CD44 in epithelial-mesenchymal transition and cancer development. Onco Targets Ther. 8:3783–3792. 2015.

30 

Li LC, Wang DL, Wu YZ, Nian WQ, Wu ZJ, Li Y, Ma HW and Shao JH: Gastric tumor-initiating CD44 (+) cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT. Oncol Lett. 10:3293–3299. 2015.

31 

Zhang W and Li Y: miR-148a downregulates the expression of transforming growth factor-β2 and SMAD2 in gastric cancer. Int J Oncol. 48:1877–1885. 2016.PubMed/NCBI

32 

Wang XH, Liu MN, Sun X, Xu CH, Liu J, Chen J, Xu RL and Li BX: TGF-beta 1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells. Tumour Biol. 37:3675–3681. 2016. View Article : Google Scholar

33 

Hoshino Y, Nishida J, Katsuno Y, Koinuma D, Aoki T, Kokudo N, Miyazono K and Ehata S: Smad4 decreases the population of pancreatic cancer-initiating cells through transcriptional repression of ALDH1A1. Am J Pathol. 185:1457–1470. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Zhao S, Ammanamanchi S, Brattain M, Cao L, Thangasamy A, Wang J and Freeman JW: Smad4-dependent TGF-beta signaling suppresses RON receptor tyrosine kinase-dependent motility and invasion of pancreatic cancer cells. J Biol Chem. 283:11293–11301. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Pan Y, Shu X, Sun L, Yu L, Sun L, Yang Z and Ran Y: miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4. Int J Oncol 50: 1965-1976, 2017.
APA
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., & Ran, Y. (2017). miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4. International Journal of Oncology, 50, 1965-1976. https://doi.org/10.3892/ijo.2017.3965
MLA
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., Ran, Y."miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4". International Journal of Oncology 50.6 (2017): 1965-1976.
Chicago
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., Ran, Y."miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4". International Journal of Oncology 50, no. 6 (2017): 1965-1976. https://doi.org/10.3892/ijo.2017.3965
Copy and paste a formatted citation
x
Spandidos Publications style
Pan Y, Shu X, Sun L, Yu L, Sun L, Yang Z and Ran Y: miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4. Int J Oncol 50: 1965-1976, 2017.
APA
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., & Ran, Y. (2017). miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4. International Journal of Oncology, 50, 1965-1976. https://doi.org/10.3892/ijo.2017.3965
MLA
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., Ran, Y."miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4". International Journal of Oncology 50.6 (2017): 1965-1976.
Chicago
Pan, Y., Shu, X., Sun, L., Yu, L., Sun, L., Yang, Z., Ran, Y."miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4". International Journal of Oncology 50, no. 6 (2017): 1965-1976. https://doi.org/10.3892/ijo.2017.3965
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team